Effects of Large Doses of Colistin Sulphomethate Sodium on Renal Function

Price, David J.; Graham, Delyth

doi:10.1136/bmj.4.5734.525

Cited by 75 publications

(54 citation statements)

References 14 publications

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“…This rate is lower than what has been reported in the literature on adults, in whom nephrotoxicity rates ranged from 17 to 100% (7,11,14; O. Sued, G. R. Kelley, A. Nenna, C. Dillon, L. Abusamra, G. de la Iglesia, H. Perez, and P. Cahn, 39th Annu.…”

contrasting

confidence: 43%

“…Similarly, Koch-Weser et al found that renal toxicity was not associated with baseline renal function as long as appropriate doses were administered (7). Large single and/or cumulative polymyxin doses have been associated with nephrotoxicity (7,14,18). In our study, older age was the only predictor of the risk of RF.…”

mentioning

confidence: 53%

“…Early reports varied widely, describing the development of renal impairment in as few as 20 to 25% and up to 100% of the patients receiving polymyxins (7,14,18). These drugs accumulate in tissues, especially the kidneys and brain, but the exact mechanism of molecular toxicity is unclear (9).…”

mentioning

confidence: 99%

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Polymyxin B Nephrotoxicity and Efficacy against Nosocomial Infections Caused by Multiresistant Gram-Negative Bacteria

Ouderkirk

Nord

Turett

et al. 2003

Antimicrob Agents Chemother

170

116

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Reported rates of nephrotoxicity associated with the systemic use of polymyxins have varied widely. The emergence of infections due to multiresistant gram-negative bacteria has necessitated the use of systemic polymyxin B once again for the treatment of such infections. We retrospectively investigated the rate of nephrotoxicity in patients receiving polymyxin B parenterally for the treatment of infections caused by multiresistant gram-negative bacteria from October 1999 to September 2000. Demographic and clinical information was obtained for 60 patients. Outcome measures of interest were renal toxicity and clinical and microbiologic efficacy. Renal failure developed in 14% of the patients, all of whom had normal baseline renal function. Development of renal failure was independent of the daily and cumulative doses of polymyxin B and the length of treatment but was significantly associated with older age (76 versus 59 years, P ‫؍‬ 0.02). The overall mortality was 20%, but it increased to 57% in those who developed renal failure. The organism was cleared in 88% of the patients from whom repeat specimens were obtained. The use of polymyxin B to treat multiresistant gram-negative infections was highly effective and associated with a lower rate of nephrotoxicity than previously described.

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contrasting

confidence: 43%

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confidence: 53%

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Polymyxin B Nephrotoxicity and Efficacy against Nosocomial Infections Caused by Multiresistant Gram-Negative Bacteria

Ouderkirk

Nord

Turett

et al. 2003

Antimicrob Agents Chemother

170

116

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“…Several reports published in the 1960s and 1970s showed that parenteral administration of polymyxin was associated with considerable nephrotoxicity (9,11,20,24). However, since their recent revival, published experiences of systemic polymyxin use suggested that the incidence of nephrotoxicity was less common and less severe than those reported 40 years ago.…”

mentioning

confidence: 70%

Characterization of Polymyxin B-Induced Nephrotoxicity: Implications for Dosing Regimen Design

Abdelraouf

Braggs

Yin

et al. 2012

Antimicrob Agents Chemother

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The increasing prevalence of multidrug-resistant Gram-negative infections has led to renewed interest in the use of systemic polymyxin B. However, the nephrotoxic properties of polymyxin B are still poorly understood. The objective of this study was to characterize nephrotoxicity associated with polymyxin B, with an emphasis on examining the impact of dosing frequencies on the onset of nephrotoxicity. Sprague-Dawley rats were divided into two groups and administered the same total daily dose of polymyxin B subcutaneously but with different dosing frequencies (either 20 mg/kg of body weight every 24 h [q24h] or 5 mg/kg q6h). Drug concentrations in renal tissue were compared between the two groups at 24 h. Kidney tissues were harvested at 48 h and compared histologically. Serum creatinine was measured daily for up to 10 days, and nephrotoxicity was defined as a significant elevation in serum creatinine (>2؋ baseline). Kaplan-Meier analysis was used to compare the onset of nephrotoxicity. Polymyxin B-induced nephrotoxicity manifested as elevation in serum creatinine and acute tubular necrosis. Extensive injury of the proximal tubules was observed. The lesions were more severe and higher drug concentrations were achieved in the kidneys of the q6h dosing group. The q24h dosing group experienced a more gradual onset of nephrotoxicity, which could be attributed to the lower kidney tissue drug concentrations (48.5 ؎ 17.4 g/g versus 92.1 ؎ 18.1 g/g of polymyxin B1, P ‫؍‬ 0.04). Preferential accumulation of polymyxin B in the kidneys suggests that uptake to renal cells is a nonpassive process and q24h dosing was less nephrotoxic than q6h dosing.

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“…As a consequence, "old" polymyxins have been revived as a last-line therapy (3,4). Two polymyxins, namely, polymyxin B and polymyxin E (synonym, colistin), have been available clinically since the late 1950s but were abandoned in the 1970s due to their potential for nephrotoxicity (5,6). There is little doubt that there is an association between polymyxin therapy and nephrotoxicity (7)(8)(9), and recent clinical studies have shown that the incidence rate is up to 60%, depending on the definition of nephrotoxicity (7,(10)(11)(12).…”

mentioning

confidence: 99%